The invention relates to the field of cell analysis, and in particular to a method of cell analysis in which the cells to be analyzed are adhesively applied to a slide and stained with a first stain, where a first digital picture is taken of the stained cells applied to the slide and then stored, where the same cells on the slide are treated with a second stain after the first digital picture is taken so that their optically measurable characteristics change, and where a second digital picture is then taken of the same cells applied to the slide and then stored.
German Patent No. DE 101 28 552 discloses an analytical method of this type and a device for performing this type of analysis. This publication describes methods and devices in which the cells to be analyzed are adhesively applied to a slide and subjected to various treatments for the purpose of ascertaining certain properties of the cells.
These treatments include in particular the “staining” of the cells, where the cells are brought into contact with a chemical substance that triggers various chemical reactions in the cells according to the properties thereof, where the chemical reactions usually precipitate in a change in optically perceivable cell properties and change the transmission, absorption and/or luminescence behavior of the cells. In the simplest case, the cells change color based on their properties allowing the cells to be separated into different categories such as normal/abnormal based on their color or the patterns of their spatial distribution of color.
In the present application, it is hereby stressed that although this application exclusively speaks of “staining” by means of a “stain”, these terms are hereinafter to be understood as all forms of treatment of the cells adhesively applied to a slide that change the emission, transmission, and/or absorption behavior of the cells in relation to electromagnetic waves, in particular in relation to electromagnetic waves with wavelengths in the visible range. “Staining” in this sense can thus also mean that the cells are exposed not to a chemical, yet rather to a physical treatment such as, for example, irradiation or heat treatment. The method described herein is especially advantageous since it describes an analysis of bodily cells that facilitates the early diagnosis of cancer with a high degree of accuracy.
It is advantageous for multiple reasons to base the diagnosis of cancer, in particular for the purpose of preventive cancer care, on the analysis of cell samples instead of tissue samples (histology, although the prevalent routine diagnostic tool today, involves interventions resulting in a loss of blood) or organ imaging (x-rays, ultrasound, etc.). The cells are the earliest manifestation of a developing cancer. The earlier the intervention is performed, the greater the chances of the disease being cured. Furthermore, cell samples are gathered by means of brush smear or fine needle biopsy and involve no loss of blood and little or no pain. Patients are therefore more readily accepting of examinations, and the examination costs are kept low.
A high degree of accuracy is required particularly in preventive care diagnostic applications. The rate of false negatives must remain low (high sensitivity) so that positive findings are not overlooked and samples are not looked upon with a false sense of security. However, the false positive rate must also remain low (high specificity), since the portion of negative cases will heavily prevail in the preventive care phase and each false positive finding leads to costly follow-up examinations or absolutely unnecessary therapy not to mention legal consequences. None of the routinely employed cytopathological diagnostic methods offers high sensitivity and specificity at the same time. Furthermore, cytopathological analyses are usually time-consuming, demand highly trained personnel and are thus costly.
The method described in DE 101 28 552 A1 has many advantages. The accuracy of the diagnosis is increased to the required degree through the fusion of cell-specific properties that are gathered in a series of analytical steps. This is achieved by having the complementary analyses performed on the same microscopic preparation by means of interposed destaining and restaining and by having the analysis values assigned to individual cells.
Nevertheless, a need exists for a method of cell analysis with high sensitivity and high specificity. The present invention meets this need.